The aim of this multidisciplinary program project is to gain a better understanding of the cellular mechanisms and interrelationships underlying chemosensory transduction and transmission of information in both human and animal model systems. Research under the auspices of the Rocky Mountain Taste & Smell Center will continue to concentrate on a cellular level analysis of structure/function relationships in gustatory and olfactory receptors. The Center comprises five laboratories in the greater Denver metropolitan area. The ionic and second messenger systems involved in transduction in taste buds will be studied with modern patch-clamp methodology. In addition, the relationship between chemospecificity and morphology of taste receptor cells will be determined. Other studies will examine the interactions between receptor cells within single taste buds. The possibility of electrical as well as chemical interactions between cells will be examined. The relationship between taste cell morphology and lineage will be studied in chimeric mice. These experiments will test whether the different morphological types of cells within taste buds represent different cell lines or different morphological manifestations of a single cell line within each taste bud. In addition, the development of taste buds will be studied to determine the sequence of origin of different cell types, synapses and opening of the taste pore. Structure/function correlation studies will examine whether the changes in chemospecificity accompanying development are mirrored by discrete anatomical changes in the receptor cell-nerve fiber interrelationships. Clinical and animal models will be utilized in studies of the olfactory epithelium. Preliminary results demonstrate unique crystalline deposits in the olfactory epithelium of presumed Alzheimer's disease patients. Examination of the patient biopsies with an KEVEX system will permit determination of the exact atomic nature of the crystals, as well as their prevalence in the biopsy material. An animal model of Alzheimer's, based on disruption of mitochondrial function, will be studied for similar histopathologic changes in the olfactory epithelium. Finally, the role of the nasal microvillar cell will be investigated further in order to test the possibility that these cells play a role in nasal chemoreceptor systems.